Melatonin-mediated β-catenin activation protects neuron cells against prion protein-induced neurotoxicity

Activation of -catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation of -catenin. In this study, melatonin increased -catenin protein expression and activation in human neuroblastoma cell lines SH-SY5Y cells. Melatonin also inhibited PrP (106-126)-induced neurotoxicity and the inhibition attenuated by treatment of -catenin inhibitor ICG-001. Activation of -catenin blocked PrP (106-126)-mediated downregulation of anti-apoptotic protein survivin and Bcl-2. Reduction of mitochondrial membrane potential, translocation of Bax, and cytochrome c release which induced by PrP (106-126) treatment were inhibited by -catenin activation, which contributed to prevented PrP (106-126)-induced neuronal cell death. In conclusion, -catenin activation by melatonin prevented PrP (106-126)-induced neuronal cell death through regulating anti-apoptotic proteins and mitochondrial pathways. These results also suggest the therapeutic value of Wnt/-catenin signaling in prion-related disorders as influenced by melatonin.